Project Summary/Abstract Fuchs? endothelial corneal dystrophy (FECD) is the most common expanded repeat disorder, affecting 4% of the US population. FECD causes progressive blindness due to premature senescence and apoptosis in corneal endothelium. Currently, the only curative treatment for FECD is a corneal transplant. This project aims to develop an understanding of the disease at a molecular level to inform the development of treatments. In 70% of late onset FECD, a CTG trinucleotide expansion in intron 2 of the TCF4 gene produces a mutant CUG RNA which can be found in foci in the nucleus of corneal endothelial cells. These mutant RNA foci are thought to cause cellular dysfunction in FECD corneal endothelial cells. This project seeks to answer the question of how a handful of molecules can have a dramatic impact on cell physiology. The first aim is to identify proteins that bind mutant CUG-repeat RNA using mass spectrometry (MS). The second aim is to identify post-translational modifications on Muscleblind-like protein (MBNL) in a FECD patient-derived cells. MBNL has been implicated by previous researchers for its propensity to CUG repeat RNA. MBNL is a splicing factor and its loss of function may explain splicing defects seen in FECD. The third aim is to validate the candidate proteins and post-translational modification results generated in aim one and aim two. The environment in the Corey laboratory is collaborative and trainees benefit from Dr. Corey?s mentorship and also the assistance of several senior researchers. This project is in collaboration with Dr. Vinod Mootha in the UT Southwestern Ophthalmology Department. There are four principal goals for this fellowship training period: 1) to be knowledgeable of the literature in RNA biology and RNA related diseases, 2) to be a proficient and successful grant and manuscript writer, 3) to be a proficient experimentalist, and 4) to be an articulate and engaging speaker to all audiences. The skills obtained through these goals will aid in the ultimate achievement of becoming a lead investigator in a research laboratory.